Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Common Atopic Dermatitis Rating Scales: A Practical Approach and Brief Review [Formula: see text].

Atopic dermatitis (AD) severity measurement scales are important in clinical trials as objective outcome measures and are often required for government and private insurance plans. These scales are sometimes underused by clinicians due to a variety of factors including time constraints and lack familiarity. We conducted a literature review on the most commonly used AD measurement scales and provide succinct user guides and scoring explanations, advantages and disadvantages, and interscale comparisons.

Brief Academic Review and Clinical Practice Guidelines for Pediatric Atopic Dermatitis.

In this clinical guidelines article, we first include a brief review of the epidemiology, pathogenesis, clinical diagnoses, and scoring-scales for pediatric atopic dermatitis (AD). We then offer a set of pharmacologic treatment guidelines for infants and toddlers (<2 years), children (2-12 years), and adolescents (>12 years). We recommend irritant avoidance and liberal emollient usage as the cornerstone of treatment in all age-groups. In infants <2 years, we recommend topical corticosteroids as first-line medication-based therapy. In infants as young as 3 months, pimecrolimus, a topical calcineurin inhibitor, may also be used. As a last resort in patients <2 years, non-traditional therapies, such as the Aron regime, may be a safer option for refractory or resistant AD before off- label medications are considered. In children and adolescents >2 years, topical corticosteroids are still considered first-line therapies, but there is sufficient safety data to utilize topical calcineurin inhibitors and topical PDE4 inhibitors as well. In children ages 2-12 years whose atopic dermatitis fails to respond to prior treatments, oral systemic immunosuppressants can be used. For adolescents >12, the biologic, dupilumab, is an additional therapeutic option. A trial of phototherapy may also be utilized in children, particularly in adolescents >12 years, if they have access to treatment. Although not currently approved for the treatment of AD, Janus-kinase (JAK) inhibitors represent a promising new class of biologics with recently completed phase III clinical trials (JADE-- MONO1/2).

From Pandemic to Progression: An Educational Framework for the Implementation of Virtual Mental Healthcare for Children and Youth as a Response to COVID-19.

COVID-19 restrictions have necessitated child/youth mental health providers to shift towards virtually delivering services to patients' homes rather than hospitals and community mental health clinics. There is scant guidance available for clinicians on how to address unique considerations for the virtual mental healthcare of children and youth as clinicians rapidly shift their practices away from in-person care in the context of the COVID-19 pandemic. Therefore, we bridge this gap by discussing a six-pillar framework developed at Hospital for Sick Children (SickKids) in Toronto, Ontario, Canada, for delivering direct to patient virtual mental healthcare to children, youth and their families. We also offer a discussion of the advantages, disadvantages, and future implications of such services.

Diagnosis and Management of Atopic Dermatitis for Primary Care Providers.

OBJECTIVE: To provide primary care providers an up-to-date approach to the diagnosis and management of atopic dermatitis (AD). QUALITY OF EVIDENCE: PubMed, Cochrane, and MEDLINE databases were searched for relevant meta-analyses, randomized controlled trials, systematic reviews, and observational studies about the diagnosis and management of AD. MAIN MESSAGE: AD is a common chronic skin disease characterized by immune dysregulation and skin barrier dysfunction. It has a substantial impact on quality of life across all ages. Despite this, AD is often still undertreated due to inaccurate diagnoses, even by many experienced dermatologists. Many primary care providers may not be aware of its commonly associated medical and psychiatric comorbidities or be familiar with new treatment options. CONCLUSION: In this clinical review, we describe the pathophysiology, epidemiology, diagnosis, and treatment of AD, specifically highlighting commonly used therapies and novel medications.

[Effect of signal transduction inhibitors on human endometrial carcinoma cells with differential PTEN gene expression].

OBJECTIVE: To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression. METHODS: PTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay. RESULTS: The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3.1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6 +/- 0.8)% and (37.8 +/- 0.8)%, respectively], the G(1) phase cells were increased to (84.1 +/- 3.2)% and (87.5 +/- 1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0 +/- 2.1)% and (49.0 +/- 1.7)%. CONCLUSION: Loss of PTEN in endometrial carcinoma cells may improve the G(1) phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.

Clinical characteristics of fulminant hepatitis in pregnancy.

AIM: To investigate the clinical characteristics of fulminant hepatitis in pregnancy. METHODS: We compared and analyzed the etiology, clinical characteristics, and laboratory examinations of 25 cases of fulminant hepatitis in pregnancy and 30 cases of fulminant hepatitis not in pregnancy. RESULTS: HBV infection and chronic fulminant hepatitis were most common both in the pregnant and in the non-pregnant groups. Jaundice, digestive tract symptoms, increase of bilirubin and thrombinogen activity were the main manifestations. The incidence of hepatic encephalopathy (HE) and hepato-renal syndrome (HRS) was significantly different between the two groups. The incidence of preterm labor, dead fetus and neonatal asphyxia was high. CONCLUSION: Fulminant hepatitis is likely to occur in late pregnancy with more severe complications, which significantly influences maternity, perinatal fetus, and newborn.

Analyses of prognostic indices of chronic liver failure caused by hepatitis virus.

AIM: To analyze the related indices about the prognoses of chronic liver failure caused by hepatitis virus. METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P = 1/(1+e(-y)) (y = 1.7262-0.0948X(1)+2.9846X(2)+0.6992X(3)+1.6019X(4)+ 2.0398X(5)). (Note: X(1)-Prothrombin activity; X(2)-digestive tract hemorrhage; X(3)-hepatic encephalopathy; X(4)-hepatorenal syndrome; X(5)-pulmonary infection.). CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

Pregnant woman with fulminant hepatic failure caused by hepatitis B virus infection: a case report.

AIM: To report the experience in successfully treating pregnant women with severe hepatitis. METHODS: Comprehensive medical treatments were performed under strict monitoring. RESULTS: Pregnant woman with severe hepatitis was successfully rescued. CONCLUSION: Vital measures taken in the treatment of pregnant women with severe hepatitis include termination of the pregnancy at a proper time and control of various complications, such as disseminated intravascular coagulation (DIC), hepatorenal syndrome, hepatic encephalopathy and infection.

Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection.

AIM: To evaluate the efficacy of hepatitis B immunoglobulin (HBIG) in interrupting hepatitis B virus (HBV) intrauterine infection during late pregnancy. METHODS: We allocated 112 HBsAg positive pregnant women into 2 groups randomly. Fifty seven cases in the HBIG group received 200 IU (unit) HBIG intramuscularly every 4 wk from the 28 wk of gestation to the time of delivery, while 55 cases in the control group received no special treatment. HBsAg, HBeAg, HBcAb, HBeAb, HBsAb and HBV DNA levels were tested in the peripheral blood specimens from all of the mothers at 28 wk of gestation, just before delivery, and in blood from their newborns within 24 h before administration of immune prophylaxis. RESULTS: The intrauterine infection rate in HBIG group and control group were 10.5% and 27.3%, respectively, with significant difference (P<0.05). It showed ascendant trend as HBV DNA levels in the peripheral blood increased before delivery. CONCLUSION: HBIG is potent to cut down HBV intrauterine infection rate significantly when administered to pregnant women regularly during late pregnancy. The possibility of HBV intrauterine infection increases if maternal blood HBV DNA> or =10(8) copies/mL.

Interruption of HBV intrauterine transmission: a clinical study.

AIM: To investigate the effect of hepatitis B virus (HBV) specific immunoglobin (HBIG) and lamivudine on HBV intrauterine transmission in HBsAg positive pregnant women. METHODS: Each subject in the HBIG group (56 cases) was given 200 IU HBIG intramuscularly (im.) every 4 weeks from 28-week (wk) of gestation, while each subject in the lamivudine group (43 cases) received 100 mg lamivudine orally (po.) every day from 28-wk of gestation until the 30(th) day after labor. Subjects in the control group (52 cases) received no specific treatment. Blood specimens were tested for HBsAg, HBeAg, and HBV-DNA in all maternities at 28-wk of gestation, before delivery, and in their newborns 24 hours before the administration of immune prophylaxis. RESULTS: Reductions of HBV DNA in both treatments were significant (P<0.05). The rate of neonatal intrauterine HBV infection was significantly lower in HBIG group (16.1 %) and lamivudine group (16.3 %) compared with control group (32.7 %) (P<0.05), but there was no significant difference between HBIG group and lamivudine group (P>0.05). No side effects were found in all the pregnant women or their newborns. CONCLUSION: The risk of HBV intrauterine infection can be effectively reduced by administration of HBIG or Lamivudine in the 3(rd) trimester of HBsAg positive pregnant women.

ABT-737 induces Bim expression via JNK signaling pathway and its effect on the radiation sensitivity of HeLa cells.

ABT-737 is a BH3 mimetic small molecule inhibitor that can effectively inhibit the activity of antiapoptotic Bcl-2 family proteins including Bcl2, Bcl-xL and Bcl-w, and further enhances the effect of apoptosis by activating the proapoptotic proteins (t-Bid, Bad, Bim). In this study, we demonstrate that ABT-737 improved the radiation sensitivity of cervical cancer HeLa cells and thereby provoked cell apoptosis. Our results show that ABT-737 inhibited HeLa cell proliferation and activated JNK and its downstream target c-Jun, which caused the up-regulation of Bim expression. Blockade of JNK/c-Jun signaling pathway resulted in significant down-regulation of ABT-737-induced Bim mRNA and protein expression level. Also, ABT-737 could evoke the Bim promoter activity, and enhance the radiation sensitivity of HeLa cells via JNK/c-Jun and Bim signaling pathway. Our data imply that combination of ABT-737 and conventional radiation therapy might represent a highly effective therapeutic approach for future treatment of cervical cancer.

Differential sensitivity of human endometrial carcinoma cells with different PTEN expression to mitogen-activated protein kinase signaling inhibits and implications for therapy.

PURPOSE: Prior studies in different tumor models have shown that, under conditions of PTEN deficiency, the mitogen-activated protein kinase (MAPK) signaling pathway appear to play a major role in the tumor cell's proliferative and survival pathway, and that pharmacological inhibition of this pathway results in tumor growth inhibition. This study aimed to explore whether sensitivity to p38MAPK inhibitors are specifically due to status of PTEN in endometrial cancer cells. METHODS: We developed a series of endometrial cancer cell lines with different PTEN expressions (Ishikawa, RL-952, HEC-1B and HEC-1A cells) or introduced the wild-type PTEN and PTEN-siRNA in four endometrial cancer cells to change its PTEN expression with a p38MAPK inhibitor, SB203580 for 2 days. Cell proliferation, cell apoptosis, and cell cycle distribution were studied, and activation of AKT, ATF-2, and p38MAPK was examined by Western blotting. RESULTS: In cultivated PTEN-deficient endometrial cancer cells, in addition to an activation of AKT, a phosphorylation of p38MAPK and ATF-2 was evident, while PTEN-positive endometrial cancer cells lacked AKT activation but revealed a reduced expression of p-p38MAPK and p-ATF-2. These PTEN-deficient endometrial cancer cells demonstrated an increased sensitivity to the anti-proliferative effects induced by SB203580 compared with the PTEN-positive endometrial cancer cells, which corresponded to alterations in cell cycle response and cell apoptosis. CONCLUSIONS: PTEN-deficient endometrial cancer cells exhibit higher p38MAPK activity, and genetic studies demonstrate that p38MAPK functions dependently of AKT. Furthermore, PTEN loss sensitizes cells to p38MAPK inhibition in endometrial carcinoma cells. These findings indicate that inhibitors of p38MAPK have the potential to be effective in the treatment of endometrial cancer patients with PTEN-deficient tumors and should be evaluated in this setting.

The use of contrast-enhanced ultrasound in uterine leiomyomas.

BACKGROUND: Ultrasound (US) is a popular method in the diagnosis and treatment of uterine leiomyomas, but the lack of accuracy greatly limits its application. Recently, microbubble enhancement technique affords direct depiction of tumor neovascularity and establishes a more precise vascular map of the tumor. This study was undertaken to describe the distribution patterns of SonoVue, a second-generation contrast agent, in the microcirculation of uterine leiomyomas, and to investigate the potential use of contrast-enhanced ultrasound (CEUS) in the characterization and treatment of uterine leiomyomas. METHODS: Ninety-six patients with uterine leiomyomas were enrolled in this study. The CEUS was performed using cadence pulse sequencing technique (CPS) and SonoVue. Enhancement patterns of different lesions were observed. The diagnostic accuracy of CEUS was compared with that of conventional ultrasound. RESULTS: After contrast injection, vessels of macro- and micro-circulation of the myoma first appeared, followed by the normal myometrium and finally the endometrium. During the washout phase, the myoma exhibited homogeneous enhancement followed by apparent hypoenhancement. The margin of the tumor was depicted clearly. There was no agent perfusion in the benign degenerative or necrotic area. However in sarcomas degeneration, the feeding vessels appeared markedly earlier than those in myometrium. In addition, the tumor exhibited heterogeneous hyperenhancment with no agent perfusion in the center and no membraniform sign was observed in the late phase. In subserous and submucous leiomyomas, the feeding arteries in the pedicle arising from the uterine could be seen. In this study, the diagnostic accuracy of CEUS and conventional US for uterine leiomyomas was 96.7% (160/165) and 82.4% (136/165) respectively. CONCLUSIONS: CEUS can provide a precise description of the leiomyomas vascularization. The specific enhancement pattern may be helpful for the characterization, treatment choice and therapeutic monitoring of leiomyomas.

Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line.

AIM: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line. METHODS: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using the 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. RESULTS: Oridonin suppressed the proliferation of the HeLa cell line in a dose- and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate- ribose polymerase cleavage. In addition, Z-D(OMe)-E(OMe)-V-D(OMe)- FMK (z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein. CONCLUSION: Our results showed that oridonin-induced apoptosis involved several molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.

[Primary study of genes related to uterine leiomyoma].

BACKGROUND & OBJECTIVE: The occurrence of uterine leiomyoma is related to the abnormal expression of some genes, but the molecular mechanism has not been clarified yet, the study screened genes related to uterine leiomyoma by comparing different genes expressed in uterine leiomyoma tissues with normal myometrium uterine tissues. METHODS: To compare different genes expressed in uterine leiomyoma tissues with normal myometrium uterine tissues by fluorescent differential display reverse transcription polymerase chain reaction (FDD-RTPCR). Four sets of anchor primers and three sets of arbitrary primers, totally twelve primer combinations, were used for FDD-RTPCR amplification. Differentially expressed cDNA fragments were cloned, sequenced, and analyzed in origin. And one of differentially expressed bands was analyzed by RT-PCR. RESULTS: Twenty-seven cDNA fragments were isolated from uterine leiomyoma. N(568) cDNA fragment shared 96% homology with the sequence of GCRG114 gene. RT-PCR confirmed that this gene was expressed lowlier in uterine leiomyoma tissues than in normal myometrium uterine tissues. CONCLUSION: N(568) cDNA fragment is highly homologous with the sequence of GCRG114 gene, and it may be related to the development of uterine leiomyoma.